We are requesting funds to purchase an Oxford Research System Nuclear Magnetic Resonance spectrometer with a 600 mm diameter magnet, wide enough to do experiments on large animals and humans. 31P, 13C and 1H high rosolution NMR experiments will be performed and the resolved peaks used to follow the concentrations and interconversion rates of intracellular metabolites, and the intracellular pH. The high resolution NMR peaks will be obtained from well defined regions in the large animals, corresponding to specific organs or tissues of interest. In these studies we will investigate the effects of different physiological insults and stresses upon the chemistry of different organs in large animals and eventually in humans. The brains of living animals will be studied under conditions of oxygen and glucose deprivation to provide a basis for understanding the chemical changes during these conditions in man. The metabolic effects induced by auditoryvisual stimulation upon human brains will be one of the first projects in humans. In human hearts and skeletal muscle the effects of intense exertion will be studied in healthy man, while in man and in animals we will evaluate the effects of hormonal stimulation. In kidneys of animals the kidney cell ATP levels during the recovery from acute renal failure will be followed. The effect of several therapeutic procedures upon recovery from renal failure will be evaluated, and when possible these studies will be extended to humans. The metabolic rate of glucose will be studied in liver and muscle in dogs and humans. The overall objective of this research is to provide biochemical understanding of the stresses experienced by humans and to explore methods of healing these injuries. The NMR spectrometer requested will provide a unique means of studying these biochemical events.